This invention relates to apparatus for and a method of mixing components, for example to effect blending of components to form a homogeneous mixture. The components will usually be in the form of powders but the invention is also applicable to the mixing of other fluent components such as liquids. Typically the components to be mixed comprise pharmaceutical actives and excipients prior to further processing thereof, e.g. tableting.
The production of homogeneous mixtures of actives and excipients is of particular importance in the pharmaceutical industry.
EP-A-0631810 discloses that in-line monitoring of the degree of homogeneity achieved in the course of blending components such as pharmaceutical actives and excipients is possible by detecting the spectroscopic characteristics of the mixture during the blending process. Where the blending process is carried out by means of a rotating mixing vessel, EP-A-0631810 teaches that the device for projecting radiation into and receiving reflected radiation from the mixture is associated with a shaft about which the vessel, specifically a V-blender, is rotated. This arrangement results in the device being located invasively with respect to the interior of the mixing vessel. The reflected radiation is conveyed to spectroscopic means located in the vicinity of the rotating mixing vessel for storage and analysis by the spectroscopic means or by a separate data acquisition and a control computer linked to the spectroscopic means.
The present invention seeks to provide improved in-line spectroscopic monitoring of mixing, especially but not exclusively blending, processes which may be non-invasive while affording greater freedom in terms of siting relative to the mixing zone.
According to one aspect of the present invention there is provided apparatus for mixing a number of components comprising a vessel for receiving the components, drive means for rotating or oscillating the vessel about an axis to effect mixing of the components within the vessel, and at least one spectroscopic monitoring means for repeatedly scanning the mixture to obtain data for use in monitoring changes in the spectroscopic profile of the mixture as mixing proceeds, the monitoring means being mounted off-axis relative to the axis about which the vessel is rotatable or oscillatable.
The monitoring means may be provided directly on-board the vessel or may instead be provided indirectly on-board the vessel as a result of being provided at least in part on a structure which rotates or oscillates with the vessel. In the former case for instance, the monitoring means may be mounted on a wall of the vessel while in the latter case the monitoring means may be carried at least in part by a frame which supports the vessel and through the agency of which the vessel is rotated or oscillated. References herein to the monitoring means being directly or indirectly on-board the vessel are to construed as referring the foregoing possibilities.
The profiles derived from scanning (hereinafter the xe2x80x9cscanned profilesxe2x80x9d) may be monitored for convergence towards a static condition. This may for example involve comparison with a predetermined target spectroscopic profile. In this context, it is to be understood that the initial spectra of the components before mixing will correspond generally to the spectrum of each of the components. As the mixing process proceeds, the spectra of the mixture will undergo change and begin to converge towards the spectra of the homogeneous mixture. Thus, the mixing process can be controlled with reference to the spectroscopic profile obtained by the monitoring means and, in particular, may be terminated when the scanned profiles meet a predetermined criterion, e.g. when the scanned profiles attain or converge towards a substantially static condition. This may for example be satisfied when the scanned profile substantially matches the target profile or when two or more scanned profiles (or parts thereof) of the mixture are substantially the same or differ from one another by no more than a predefined extent.
Where used, the target profile may be representative of a selected condition of the mixture; for instance, it may be representative of the homogeneous end-point for a mixture of the components undergoing blending or an intermediate state lying between the homogeneous end point and the unmixed state.
Often the components undergoing mixing will have different chemical compositions. However, the invention also encompasses the mixing of components having the same or substantially the same chemical composition. For example, the apparatus of the invention may be used for mixing components which have the same or substantially the same chemical composition but have differing physical characteristics, such as moisture content, particle distribution etc. Thus, one application of the invention lies in the combining of two fractions of the same material, one fraction comprising fines and the other comprising coarser particles, the mixing process being carried out to produce a mixture in which the fines are dispersed into the coarser particles, e.g. to secure a substantially uniform distribution of fines in the mixture.
Control means responsive to the monitoring means may be provided for controlling the mixing process.
Thus, the drive means may be controlled by the control means in dependence upon the result of the comparison so that the mixing process can be terminated when the profiles derived from scanning converge on or substantially match the predetermined profile or converge towards a static condition where the changes in scanned profiles (or parts thereof are no greater than a predefined extent.
The monitoring means may include or be associated with comparison means for comparing spectroscopic profiles corresponding to the scanning-derived data with the target profile or previously derived scanned profiles obtained during a given mixing cycle. Thus, the monitoring means may embody the comparison means so that the comparison of scanned profiles with target profile or previously derived scanned profiles is effected during rotation or oscillation of the monitoring means with the vessel.
When the scanned profiles have converged to a predetermined extent towards a static condition (e.g. when a desired level of matching between the scanned profile and a target profile is obtained), the monitoring means may be arranged to supply an output signal to signal utilising means for controlling the mixing process. For instance, the signal utilising means may be operable in response to receiving the output signal to terminate the mixing process by suitable control of the drive means, e.g. by disabling the drive means and terminating rotary or angular movement of the vessel.
In an alternative embodiment, the comparison means may be separate from the monitoring means and the vessel. In this case, data transferring means will be provided for transferring scanning-derived data from the monitoring means to the comparison means. The data transferring means may for example comprise a signal transmitter directly or indirectly on-board the vessel and a receiver associated with the comparison means whereby the data is transmitted radiatively from the monitoring means to the comparison means.
Matching of the newly derived scanned and target or previously obtained scanning profiles (at least to the desired extent) conveniently leads to automatic termination of the mixing process. However, we do not exclude the possibility that such matching, whether carried out directly or indirectly on-board the vessel or elsewhere, may instead give rise to an output signal, e.g. visual or audible, suitable for attracting an operator""s attention to the fact that mixing to an acceptable level, e.g. an acceptable level of homogeneity, has been secured and that the mixing process can be terminated and the mixture transferred to a subsequent processing stage.
The monitoring means is preferably self-powered and to this end conveniently includes a power source which may be in the form of one or more batteries, preferably rechargeable batteries.
Where comparison of the newly derived profiles and target or previously derived profiles is carried out directly or indirectly on-board the vessel, the monitoring means may include data storage means for storing the scanning-derived data, optinally together with at least one predetermined target profile where applicable. The scanning-derived data collected during the course of a mixing process may then, during or on completion of a mixing cycle, be transferred to separate data acquisition means to allow a record to be maintained for a series of mixing cycles.
The monitoring means conveniently includes a signal transmitter for transmitting signals radiatively to a receiver located in the vicinity of or remotely from the vessel thereby eliminating hard-wired connections (such as electrical conductors, optical fibres and the like) between the monitoring means and signal utilising means and/or a data acquisition means linked to the receiver. For instance, the transmitted signal may be in the form of a radiation signal such as a radio frequency signal.
In a preferred embodiment, the monitoring means comprises a self-contained unit capable of being battery-powered and is provided with means for detachably docking the unit with the vessel, preferably non-invasively, or with structure which rotates or oscillates with the vessel so that the scanning means is in registry with a window through which spectroscopic data is obtained.
Where the monitoring means is battery powered, the battery supply may form part of the self-contained unit or it may comprise a separate unit which may be provided directly or indirectly on-board the vessel. In this event, because the battery supply unit and the monitoring means both rotate or oscillate with the vessel, there may be a hard-wired connection between the two.
The self-contained unit will typically comprise at least the scanning means, a radiative signal transmitter, and optionally a compartment or compartments containing or for reception of a battery or batteries for powering the unit. In addition, the self-contained unit may include data storage means and said comparison means; for instance, the data storage means and the comparison means may both be embodied in a microprocessor or computer forming part of the unit.
The self-contained unit is conveniently docked with the vessel in registry with the window by means of releasable, preferably quick-release, devices, e.g. in the form of one or more latching devices co-operating with a keeper or keepers. The releasable devices are preferably arranged to clamp the unit securely to the vessel. One form of suitable device comprises a sprung draw latch commercially from Southco Europe Limited of Cheltenham, England.
Instead of being mounted for rotation or oscillation with the vessel, the monitoring means may be located at a fixed position, the arrangement being such that the monitoring means xe2x80x9cviewsxe2x80x9d the contents of the vessel at least during part of its cycle of rotation or oscillation. Thus, for example, the vessel may be provided with a window through which monitoring means xe2x80x9cviewsxe2x80x9d the contents of the vessel as the window traverses the line of sight of the monitoring means. The window may be strategically located at that part of the vessel which makes the closest approach to the monitoring means during each cycle of rotation or oscillation of the vessel and the window may be of elongated configuration in the direction of travel past the monitoring means so as to afford an extended interval of xe2x80x9cviewingxe2x80x9d.
The monitoring means may be operable at only predetermined points during each cycle of rotation or oscillation of the vessel.
Means may be provided to sense the angular position of the vessel with respect to a datum position and, if desired, control operation of the monitoring means so that data relating to the mixture is only collected at said predetermined points. The monitoring means may be disabled at other times. Such predetermined points may for instance correspond to points during said cycle when the mixture can be expected to be in contact with the wall of the vessel at the location xe2x80x9cviewedxe2x80x9d by the monitoring means.
A preferred alternative however is to arrange the monitoring means to collect data substantially continuously throughout the cycle of rotation or oscillation (e.g. at the rate of one scan per second) and, from the data collected, discriminate between data corresponding to the points in the cycle when the mixture makes suitable contact with the window, i.e. data representative and data unrepresentative of the state of mixing. In this case, it may not be necessary to provide means for determining the angular position of the vessel.
Particularly but not necessarily exclusively where the monitoring means is fixed relative to the moving vessel, the vessel may, with respect to the radiation used for monitoring, be substantially transparent over an extended or substantially the entire area thereof.
The walls of the vessel may be fabricated at least in part, e.g. at least a major part and possibly substantially entirely, from a plastics material. The plastics material may be one which is transparent with respect to the radiation used (e.g. near infra red radiation).
While the vessel will normally comprise a rigid structure, usually of metal such as stainless steel, we do not exclude the possibility of the vessel being constituted by a flexible bag, e.g. of a plastics material. The bag and monitoring means may be adapted to enable the monitoring means to be coupled to the bag or the monitoring means may be mounted separately from the bag either in fixed relation to the bag or on a structure that rotates or oscillates with the bag, as described above.
Various other aspects of the invention are indicated below which other aspects may, where the context admits, be combined with each other and/or with said one aspect and/or any of the other features defined above.
According to a second aspect of the present invention there is provided apparatus for mixing a number of components (for example to produce a homogeneous mixture), comprising a vessel for receiving the components, drive means for rotating or oscillating the vessel about an axis to effect mixing of the components within the vessel, and at least one spectroscopic monitoring means provided directly or indirectly on-board the vessel for repeatedly scanning the mixture to obtain data for use in monitoring changes in the spectroscopic profile of the mixture as mixing proceeds, the monitoring means being in the form of a self-contained unit mounted releasably on the vessel.
According to a third aspect of the present invention there is provided apparatus for mixing a number of components (for example to produce a homogeneous mixture), comprising a vessel for receiving the components, drive means for rotating or oscillating the vessel about an axis to effect mixing of the components within the vessel, and at least one spectroscopic monitoring means provided directly or indirectly on-board the vessel for repeatedly scanning the mixture to obtain data for use in monitoring changes in the spectroscopic profile of the mixture as mixing proceeds, the monitoring means including means for radiatively transmitting to an off-board receiver an output for use in controlling the mixing process.
According to another aspect of the invention there is provided apparatus for mixing a number of components (for example, to produce a homogeneous mixture), comprising a mixing zone for receiving the components, means for mixing of the components within the mixing zone, and at least one spectroscopic monitoring means for repeatedly scanning the mixture within and/or downstream of the mixing zone to obtain and record data for use in monitoring changes in the spectroscopic profile of the mixture as mixing proceeds, means responsive to the monitoring means for modifying, e.g. terminating, the mixing process when the spectroscopic data obtained signifies attainment of a desired level of mixing and data acquisition means for collecting recorded data from the monitoring means, the data acquisition means having a docking station with which the monitoring means can be docked on completion of the mixing process to allow transfer of recorded data from the monitoring means to the data acquisition means.
To facilitate docking the monitoring means is preferably in the form of a portable unit, e.g. hand portable, adapted for detachable mounting on a wall of the mixing zone so that, on completion of the mixing cycle, the monitoring means can be dismounted and transported, e.g. manually, to the docking station. For the purposes of portability, the unit incorporating the monitoring means will usually conform with HSE Manual Handling Operations Regulations 1992 and will typically be no more than 25 kg in weight, preferably less.
A guide rail or rails may be provided on the vessel for locating the unit in a desired position, e.g. with the monitoring means properly registered with the window, so that the unit may initially be engaged with the guide rail(s) and then adjusted by sliding the same along the rail(s) to the desired position before securing it in that position with the aid of releasable fastening devices.
The docking arrangement may include one or more hook formations on the unit and a support or supports on the vessel so that the unit can be offered up to the vessel by hooking the hook formation(s) to the support(s) which may comprise a rail to permit sliding adjustment of the unit after engaging the hooks with the rail. In this way, the unit may be temporarily suspended from the support(s) to free the hands of the operator and thereby allow him to operate a fastening device or devices to secure the unit in place so that the unit is held in place by the hook formation(s)/support and the fastening device(s).
The monitoring means may be provided with one or more handles to aid manipulation during detachment from the wall of the mixing zone, docking with the data acquisition means and/or transport between the mixing zone and the data acquisition means.
The rotatable or oscillatable mixing vessel may comprise a so-called V-blender of the type described in EP-A-0631810, the relevant disclosure of which is incorporated herein by this reference.
Alternatively, and more preferably, the rotatable or oscillatable mixing vessel may comprise a so-called Intermediate Bulk Container (IBC) designed for use in conjunction with an installation comprising a drive unit and a mounting frame for receiving and supporting the IBC, the mounting frame being coupled with the drive unit for rotation about an axis to effect tumbling of the components within the IBC as the latter rotates with the mounting frame.
In accordance with another aspect of the present invention there is provided an IBC provided with a window allowing for the scanning of the contents thereof by spectroscopic monitoring means, preferably near infrared spectroscopic monitoring means.
In accordance with a further aspect of the invention there is provided an IBC provided with docking means for the releasable mounting of a spectroscopic monitoring means for the scanning of the contents of the IBC.
Also in accordance with the invention there is provided an IBC provided with a spectroscopic monitoring means for the scanning of the contents of the IBC, the monitoring means preferably being non-invasively mounted on the IBC in registry with a window through which the scanning radiation is transmitted.
Usually the IBC is in the form of a hopper, typically of generally rectangular cross-section, with an inlet for components to be mixed at a large cross-section upper part of the IBC and an outlet for discharge of the mixture at a somewhat smaller cross-sectional lower part.
The IBC may be provided with means for coupling the same to a drive unit for rotating or oscillating the IBC, usually about an axis which extends obliquely with respect to the IBC, e.g. such that the axis of rotation or oscillation does not intersect the axis about which the IBC is generally symmetrical.
The IBC is conveniently transportable; for instance, it may be provided with ground-engaging wheels or may be adapted for mounting on a wheeled vehicle such as a trolley.
The coupling between the IBC and the drive unit may be through the agency of a mounting frame associated with the IBC or the drive unit.
Where the mounting frame is associated with the drive unit, the frame may comprise upper and lower sections which are relatively movable towards and away from one another between a loading position in which the IBC may be introduced into the mounting frame and a clamping position in which the IBC is raised out of contact with the ground and securely clamped for rotation with the frame.
The frame may be supported from a shaft of the drive unit for rotation about an axis which is obliquely orientated with respect to a central axis of the frame whereby the IBC and its contents are rotated an axis which is oblique with respect to the axes about which the IBC is generally symmetrical. The axis of rotation for instance may be substantially horizontal and the mounting frame may have a generally horizontal axis about which it is substantially symmetrical and which is inclined in a horizontal plane with respect to the rotational axis of the drive means, e.g. at an angle which may range from about 10xc2x0 to about 40xc2x0, with 17xc2x0 and 30xc2x0 being typical angles of obliqueness.
While the monitoring means is preferably provided directly on the IBC, we do not exclude the possibility that the monitoring means may be provided on the mounting frame and arranged to effect monitoring the contents of the IBC, e.g. through a strategically located window provided in a wall of the IBC.
According to a further aspect of the present invention there is provided apparatus for mixing a number of components (for example to produce a homogeneous mixture), comprising a housing having an inlet and an outlet for receiving the components and means for effecting feed of the components from the inlet to the outlet while effecting mixing thereof, means for feeding the components to the inlet while mixing is taking place and means for collecting the mixture from the outlet while mixing is taking place, the housing being provided with at least one near infrared spectroscopic monitoring means for repeatedly scanning the mixture within the mixing zone and/or downstream thereof to obtain data for use in monitoring changes in the spectroscopic profile of the mixture.
The monitoring means may be arranged to scan the mixture in the mixing zone and/or a point downstream of the outlet, e.g. in a conduit connected to receive the mixed components from the mixing zone.
In this last-mentioned aspect of the invention, the monitoring means may be deployed to scan the mixture at a location along the path of travel through the housing and/or downstream of the outlet where the mixture would normally be expected to be in the desired state, e.g. substantially homogeneous, and comparison means may be provided for comparing the scanned spectroscopic profile of the mixture with previously obtained scanned profiles or with a predetermined target profile representing the desired state, e.g. homogeneous end point, for the mixture. In this way, if the comparison indicates that the mixture has not attained the desired state, the mixing process can be modified or terminated to allow remedial action to be taken.
In one embodiment of the invention according to this aspect of the invention, the mixing zone is within a stationary housing and mixing is effected by means of a rotatable or angulary oscillatable mixing device which also serves to feed the mixture of components towards the outlet.
The monitoring means employed in the present invention is preferably a near infra red spectroscopic unit having a solid state tunable filter, such as an acoustic-optic tunable filter.
The invention also resides in a method of mixing including, inter alia, the following aspects considered individually or, where the context admits, in combination with each other and/or in combination with aspects and features of the invention referred to above:
A method of mixing a number of components (for example to produce a substantially homogeneous mixture thereof) comprising introducing the components into a mixing vessel, rotating or oscillating the mixing vessel to effect mixing of the components and non-invasively monitoring mixing by collecting spectroscopic data from the mixture during rotation or oscillation of the vessel.
A method of mixing a number of components (for example to produce a substantially homogeneous mixture thereof) comprising introducing the components into a mixing vessel, rotating or oscillating the mixing vessel to effect mixing of the components, monitoring mixing by collecting and optionally analysing spectroscopic data from the mixture by means of spectroscopic monitoring means which rotates or oscillates with the vessel.
A method of mixing a number of components (for example to produce a substantially homogeneous mixture thereof) comprising introducing the components into a mixing vessel which has an axis about which it is substantially symmetrical, rotating or oscillating the mixing vessel about an axis which extends obliquely relative to said vessel axis to effect mixing of the components and monitoring mixing by collecting spectroscopic data from the mixture during rotation or oscillation of the vessel.
A method of mixing a number of components (for example to produce a substantially homogeneous mixture thereof) comprising introducing the components into an IBC, rotating or oscillating the IBC to effect mixing of the components and monitoring mixing by collecting spectroscopic data from the mixture.
A method of mixing a number of components (for example to produce a substantially homogeneous mixture thereof) comprising introducing at least one of the components into a mixing zone, in a first phase of operation effecting mixing while monitoring the condition of said at least one component by collecting spectroscopic data representative of such condition, on detection that said at least one component has attained a desired condition adding at least one additional component to the mixing zone and, in a second phase of operation, effecting mixing while monitoring the condition of the mixture as supplemented with said additional component by collecting spectroscopic data representative of such condition to determine the attainment of a desired condition of said supplemented mixture.
The above aspect of the invention may be carried out in a rotating or oscillating vessel or it may be carried in a non-rotating vessel or conduit provided with mixing means such as a bladed rotor or an orbiting screw mixer. In the case of a non-rotating vessel or conduit, the material may be fed continuously through the mixing zone and the additional component or components may be introduced at one or more locations downstream of the point of introduction of said at least one component.
A method of mixing a number of components (for example to produce a substantially homogeneous mixture thereof) comprising introducing at least one of the components into a mixing vessel, in a first phase of operation rotating or oscillating the vessel while monitoring the condition of said at least one component by collecting spectroscopic data representative of such condition, on detection that said at least one component has attained a desired condition adding at least one additional component to the mixing vessel and, in a second phase of operation, rotating or oscillating the vessel while monitoring the condition of the mixture as supplemented with said additional component by collecting spectroscopic data representative of such condition to determine the attainment of a desired condition of said supplemented mixture.
A typical application lies in mixing pharmaceutical components where one of the components comprises a lubricant such as magnesium stearate. Care has to be exercised in ensuring that the lubricant does not fully coat the particles of said pharmaceutical components (sometimes referred to as overblending) otherwise subsequent tabletting of the mixture is not possible. Thus, in the last two mentioned aspects of the invention, the first phase may comprise partial blending of the pharmaceutical components in the absence of the lubricant component, while the second phase may comprise addition of the lubricant component and completion of blending with the excipients and active to a desired level of homogeneity (but without overblending).
In the foregoing, two phases of mixing while collecting spectroscopic data are mentioned but it will be appreciated that there may be more than two such phases. For instance, there may be a further phase or phases in which a further component or components are added and mixing continued while collecting spectroscopic data allowing the attainment of the desired condition to be determined.
The condition monitored in the first phase may be of the same nature as that for monitored during the second stage. For example, in both phases, the condition monitored may be related to the level of homogeneity attained, i.e. substantially fully homogeneous or an acceptable level lying between for instance the fully inhomogeneous and the fully homogeneous states.
However, the conditions monitored need not be of the same nature. For instance, in the first phase, the components introduced may be in the form of fines and coarser particles and the first phase may comprise monitoring the extent of distribution of fines within the mass of coarse particles while the second phase, after introduction of the additional component(s), may involve monitoring for the attainment of the homogeneous endpoint or some other acceptable level of blending.
It will be appreciated that, where the context admits, the various method aspects of the invention may be carried out using the various aspects and features of the apparatus and/or IBC as described above. In particular, the method of the invention in its various aspects is preferably carried out using an acoustic optic tunable filter (preferably one based on a tellurium dioxide crystal) to produce, from a broad band radiation source (preferably a near infra red source), radiation at a wider range of different wavelengths or within different bands.